Reduced tumorigenicity of human gastric carcinoma cells engineered to produce IL-2 in SCID mice reconstituted with peripheral blood cells from cancer patients.
We have examined the validity of a humanized immune system with an animal model to assess cytokine gene therapy for cancer patients. For that purpose, we prepared hematologically-reconstituted severe combined immunodeficiency mice by transferring patient's peripheral blood cells containing CD34+ cells. These animals were inoculated subcutaneously with human gastric cancer lines transduced with cytokine genes. Tumorigenicity of interleukin-2-producing cells was significantly reduced in reconstituted but not in non-reconstituted mice, whereas that of wild-type and interleukin-6 producer cells was not affected irrespective of the reconstitution status. An inability to induce protective immunity in the reconstituted mice, which had rejected interleukin-2-producers, suggested that the effector cells mediating the antitumor response were non-T cells of donor origin. The experimental system presented in this study seems to be a feasible model to investigate applicable cytokines for patients.
Tagawa
M
M
Division of Pathology, Chiba Cancer Center, Japan. mtagawa@biolab.kazusa.or.jp
Goto
S
S
Takenaga
K
K
Takeshita
A
A
Saotome
T
T
Takenouchi
T
T
Tsurumachi
T
T
Gunji
Y
Y
Matsubara
H
H
Sakiyama
S
S
D000328:Adult; D000818:Animals; D002277:Carcinoma / Q000276:immunology*; D005260:Female; D006801:Humans; D007109:Immunity; D007376:Interleukin-2 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000276:immunology*; D014183:Transplantation, Heterologous
D007376:Interleukin-2